title: Autoantibodies to low-density lipoprotein receptor-related protein 4 in myasthenia gravis.
abstract: Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction, where acetylcholine receptor (AChR), muscle-specific kinase (MuSK), and low-density lipoprotein (LDL) receptor-related protein 4 (Lrp4) are essential. About 80% and 0% to 10% of patients with generalized MG have autoantibodies to AChR and MuSK, respectively, but pathogenic factors are elusive in others. Here we show that a proportion of AChR antibody-negative patients have autoantibodies to Lrp4. These antibodies inhibit binding of Lrp4 to its ligand and predominantly belong to the immunoglobulin G1 (IgG1) subclass, a complement activator. These findings together indicate the involvement of Lrp4 antibodies in the pathogenesis of AChR antibody-negative MG.
authors.affiliation: Division of Genetics, Department of Cancer Biology, the Institute of Medical Science, the University of Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Higuchi
authors.forename: Johko
authors.initials: J
authors.lastname: Hamuro
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Motomura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamanashi
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D026502:LDL-Receptor Related Proteins / Q000276:immunology*; D009157:Myasthenia Gravis / Q000276:immunology*; D015531:Radioimmunoprecipitation Assay; D011950:Receptors, Cholinergic / Q000276:immunology
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D026502:LDL-Receptor Related Proteins; D011950:Receptors, Cholinergic